Search results for "PDX"
showing 6 items of 6 documents
Preclinical models for precision oncology
2018
Precision medicine approaches have revolutionized oncology. Personalized treatments require not only identification of the driving molecular alterations, but also development of targeted therapies and diagnostic tests to identify the appropriate patient populations for clinical trials and subsequent therapeutic implementation. Preclinical in vitro and in vivo models are widely used to predict efficacy of newly developed treatments. Here we discuss whether, and to what extent, preclinical models including cell lines, organoids and tumorgrafts recapitulate key features of human tumors. The potential of preclinical models to anticipate treatment efficacy and clinical benefit is also presented,…
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′‐phosphate supplementation
2019
OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating sc…
Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours.
2016
AbstractTreatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich bloo…
Capturing colorectal cancer inter-tumor heterogeneity in patient-derived xenograft (PDX) models
2019
Patient‐derived xenograft (PDX) models have become an important asset in translational cancer research. However, to provide a robust preclinical platform, PDXs need to accommodate the tumor heterogeneity that is observed in patients. Colorectal cancer (CRC) can be stratified into four consensus molecular subtypes (CMS) with distinct biological and clinical features. Surprisingly, using a set of CRC patients, we revealed the partial representation of tumor heterogeneity in PDX models. The epithelial subtypes, the largest subgroups of CRC subtype, were very ineffective in establishing PDXs, indicating the need for further optimization to develop an effective personalized therapeutic approach …
Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups☆
2013
Background Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality. Objectives To assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups. Material and methods Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8–12 h prior to delivery and reset to 21% 6–8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glut…
Estudio de la heterogeneidad fenotípica del sarcoma de Ewing en xenotrasplantes
2019
Los Tumores de la Familia del Sarcoma de Ewing (TFSE) son neoplasias malignas de hueso y de partes blandas, poco frecuentes (entre el 6-8% de los tumores malignos primarios de hueso) y que afectan principalmente a pacientes en edad de crecimiento, adolescentes y adultos jóvenes (1, 2). El término engloba a tres tumores que durante años han sido considerados por separado por su morfología característica, pero que forman un espectro morfológico, de biología e histogénesis comunes (3). Dichos tumores son los Sarcomas de Ewing clásicos, los atípicos y los tumores neuroectodérmicos primitivos periféricos (PNET). Desde el punto de vista morfológico son neoplasias constituidas por células pequeñas…